Safety Study of Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

Phase 1

Completed

• Conditions: Carcinoma, Colorectal
• Interventions: Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)

• Registration Number: NCT01380600
• Lead Sponsor: Jennerex Biotherapeutics

Brief Summary

The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously every 2 weeks in colorectal carcinoma patients who are refractory to or intolerant of oxaliplatin, irinotecan, and Erbitux treatments.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2011-06-22
• Study First Submitted QC: 2011-06-22
• Study First Posted: 2011-06-27
• Status Verified: 2012-03
• Primary Completion: 2012-11
• Study Completion: 2015-12
• Last Update Submitted: 2016-01-06
• Last Update Posted: 2016-01-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Histologically-confirmed, advanced/metastatic colorectal carcinoma
• Failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease (if tumor advanced either immediately or within 3 months of the end of treatment)
• Resistance to Erbitux: patients with Ras mutations, or for whom Erbitux has failed (if tumor advanced either immediately or within 3 months of the end of treatment, or there is no response to Erbitux therapy due to a lack of expression of EGFR (epidermal growth factor))
• Karnofsky Performance Score (KPS) ≥ 70
• Age ≥18 years
• Laboratory Safety: WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3, ANC ≥ 1,500 cells/mm3, Hemoglobin ≥ 10 g/dL (transfusion allowed), Platelet count ≥ 100,000 plts/mm3,Total bilirubin ≤ 1.5 X ULN, INR ≤ 1.5, AST, ALT ≤ 2.5x ULN (in case of liver metastasis: AST,ALT ≤5.0 x ULN)
• Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline phosphatase) - If patients are diabetic, a fasting glucose must be done and patients must be > 160 mg/dL.
• Patients who, if they are sexually active, are willing and able to refrain from sexual activity for 3 weeks following JX-594 administration. Patients who are willing and able to use a permitted contraceptive for 3 months after the final administration of JX-594.

Exclusion Criteria

• Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
• Known myeloproliferative disorders requiring systemic therapy
• History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy
• History of acquiring opportunistic infections.
• Tumor(s) invading a major vascular structure (e.g. carotid artery)
• Tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur
• Clinically uncontrolled and/or rapidly accumulating ascites, pericardial and/or pleural effusions
• History of severe or unstable cardiac disease
• Current, known CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed)
• Administered anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
• Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.] Low dose aspirin (approximately 81 mg) allowed.
• Pulse oximetry O2 saturation <90% Pulse oximetry O2 saturation <90% at rest
• Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
• Pregnant or nursing
• Household contact exclusions:
• Women who are pregnant or nursing an infant
• Children < 5 years old
• People with skin disease (e.g. eczema, atopic dermatitis, and related diseases
• Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including AIDS, organ transplant recipients, hematologic malignancies)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm; Dose escalation	Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)	Dose escalation 1e6 pfu/kg bw, 1e7 pfu/kg bw, 3e7 pfu/kg bw of Recombinant Vaccinia GM-CSF JX-594

Primary Outcome Measures

Name	Time	Method
Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by biweekly intravenous (IV) infusion	DLT evaluations through 14 days following last JX-594 treatment	Any of the following treatment related adverse events: Grade 4 toxicity, Grade 3 hematologic toxicity for \> 5 days, Grade 3 non-hematologic toxicities persisting for \> 7 days except for flu-like symptoms that respond to standard therapies.
Determine the safety of JX-594 administered by biweekly IV infusion	Safety evaluations through 28 days after last dose of JX-594	Adverse events will be collected and assessed to assess safety and tolerability through 28 days after last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).

Secondary Outcome Measures

Name	Time	Method
Determine the anti-tumoral response of JX-594	Disease control and response assessment at Week 8	Tumor response (Stable, partial, complete, progression) by standard RECIST on CT/MRI. Decrease in tumor blood marker.
Determine the pharmacokinetics, pharmacodynamics and immune response activity of JX-594	Blood samples collected at assigned time points from baseline through Week 8	Change over time in viral genomes, infectious units, GM-CSF concentration, peripheral white blood cell counts, plasma cytokine measurements, and neutralizing antibodies to JX-594 in blood and/or serum.

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of